tbuckley/cabot-search huggingface dataset:
Abstract 12912: Metabolic Labeling of Cardiomyocyte-Derived Small Extracellular-Vesicle (sEV) MiRNAs Identifies MiR-208a in Cardiac Regulation of Lung Gene Expression
Authors: Chaoshan Han, Junjie Yang, Eric Zhang, qinkun zhang, Hind Lal, Prasanna Krishnamurthy, Jianyi J Zhang, Gangjian Qin
Journal: Circulation (2022)

Background &amp; Hypothesis: T. gondii uracil phosphoribosyltransferase (UPRT) can convert 4-thiouracil(4TUc) into 4-thiouridine (4TUd), thus incorporating into nascent RNAs, and the thio-labeled RNAs can be identified by thio-linked-biotinylation and streptavidin-affinity isolation, we hypothesize that cardiomyocyte (CM) expression of UPRT ( CM UPRT) allows labeling and tracking of CM-derived miRNAs in PB sEV and peripheral organs. Methods &amp; Results: We generated mice that expressed T. gondii UPRT only in cardiomyocytes ( CM UPRT mice) and tested our hypothesis that CM-derived miRNAs ( CM miRs) are transferred into remote organs after myocardial infarction (MI) by PB sEV. We found that 4TUd was incorporated with high specificity and sensitivity into RNAs isolated from the hearts and PB sEV of CM UPRT mice six hours after 4TUc injection. In PB sEV, 4TUd was incorporated into CM-specific/enriched miRs including miR-208a, but not into miRs with other organ or tissue-type specificities. 4TUd-labeled miR208a was also present in lung tissues, especially lung endothelial cells (ECs), and CM-derived miR-208a ( CM miR-208a) levels peaked 12 hours after experimentally induced MI in PB sEV and 24 hours after MI in the lung. Notably, miR-208a is expressed from intron 29 of α myosin heavy chain (αMHC), but αMHC transcripts were nearly undetectable in the lung. When PB sEV from mice that underwent MI (MI- PB sEV) or sham surgery (Sham- PB sEV) were injected into intact mice, the expression of Tmbim6 and NLK, which are suppressed by miR-208a and cooperatively regulate inflammation via the NF-κB pathway, was lower in the lungs of MI- PB sEV-treated animals than the lungs of animals treated with Sham- PB sEV or saline. In MI mice, Tmbim6 and NLK were downregulated, whereas endothelial adhesion molecules and pro-inflammatory cells were upregulated in the lung; these changes were significantly attenuated when the mice were treated with miR-208a antagomirs prior to MI surgery. Conclusion: CM UPRT mice enables us to track PB sEV-mediated transport of CM miRs and identify an miR-208a-mediated mechanism by which myocardial injury alters the expression of genes and inflammatory response in the lung.
Abstract 13914: Additional ASCVD Risk Factors for Patients With Diabetes: FIB-4 Score and NLR Are Higher in Adults With Diabetes and Current Risk Enhancers vs No Risk Enhancers in Real-World Evidence
Authors: Himal Chapagain, Yousef Alish, Michael Becich, Alison Bradley, Soledad Fernandez, Dan Ford, Wenke Hwang, Jong Jeong, Martha Jurczak, H Lester Kirchner, Kathleen M McTigue, Richard Morgan, Anuradha Paranjape, Neena Thomas, David Williams, Jonathan Arnold
Journal: Circulation (2022)

Introduction: Obesity, chronic inflammation, and elevated levels of atherogenic lipids have been associated with increased risk of ASCVD events. Current AHA/ACC guidelines identify existing risk enhancers for ASCVD including persistently elevated LDL-C or triglycerides, chronic kidney disease, chronic inflammatory conditions, and elevated inflammatory markers. Hypothesis: We hypothesized that in a population-level study of adults with diabetes mellitus (DM) without a history of prior ASCVD events, the average body mass index (BMI), hepatic fibrosis score (FIB-4), and neutrophil to lymphocyte ratio (NLR) are higher in the cohort of patients with other, AHA-identified ASCVD risk enhancers. Methods: We performed a hypothesis-driven secondary analysis using a cross-sectional dataset of EHR data from 7 health systems participating in PaTH, a Partner Network in PCORnet. Adults over 40 with DM and without ASCVD were included if they had LDL-c assessed in the most recent year of available data and had &gt;6 months of pre-index data available. We describe cohort-level averages and standard deviations of the most recent lab values and clinical measurements for cohorts with and without AHA/ACC defined ASCVD risk enhancers. Results: We identified 50,749 patients in our baseline risk cohort and 67,593 patients in our enhanced risk cohort across the 7 sites. The enhanced risk cohort had a higher mean (SE) BMI 34.1 (0.28) vs 33.7 (0.29) kg/m2, FIB-4 score 1.5 (0.01) vs 1.4 (0.01) and NLR 62.5 (0.24) vs 61.2 (0.23) compared to the baseline risk cohort. NLR and FIB-4 demonstrated consistently higher averages in the enhanced-risk cohorts across sites. Conclusions: FIB-4 score and NLR both have higher population averages in cohorts with other markers of enhanced ASCVD risk in an adult diabetic patient population. The role of these markers in independently predicting ASCVD risk should be further explored with adjusted analyses in longitudinal datasets.
Abstract 13453: Caffeine and Development of Gestational Diabetes Mellitus and Preeclampsia: The Boston Birth Cohort
Authors: Tae Eun Kwon, Tiange Liu, Xiaobin Wang, Xiumei Hong, Noel T Mueller
Journal: Circulation (2022)

Introduction: Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common pregnancy complications. Some studies have linked self-reported caffeinated coffee and tea intake to lower risks of GDM and PE. But little is known about the associations of objectively measured caffeine exposure during pregnancy with GDM and PE. Methods: We used data from pregnant women without pre-existing diabetes or hypertension in the Boston Birth Cohort (enrolled 1998-2016). From cord blood and maternal blood, collected within 72 hours after delivery, we measured caffeine metabolites (caffeine, 1,7-dimethyluric acid, and 3-methylxanthine). We also estimated caffeinated coffee and tea intake in each trimester from a food frequency questionnaire. We examined odds ratios of GDM and PE using logistic regression models after adjusting for confounders. We modeled metabolites in tertiles and continuously and beverage intakes in categories: 0; 1-6 cups/week; ≥7 cups/week. Results: In cord blood analyses (n=744; 8% with GDM; 7% with PE), each 1-SD increments in cord caffeine, 1,7-dimethyluric acid, and 3-methylxanthine were associated with 0.71 (95% CI: 0.53, 0.94), 0.80 (95% CI: 0.59, 1.08) and 0.61 (95% CI: 0.43, 0.86) times the odds of GDM, respectively. In maternal blood analyses (n=1097; 8% with GDM; 8% with PE), each 1-SD increments in maternal caffeine and 1,7-dimethyluric acid were associated with 0.81 (95% CI: 0.64, 1.02) and 0.87 (95% CI: 0.68, 1.11) times the odds of GDM, respectively. Caffeine metabolites in cord or maternal blood were not statistically associated with PE. Self-reported coffee intake of ≥7 cups/week was significantly associated with lower odds of GDM (in all trimesters) and lower odds of PE (in 3 rd trimester) than no coffee intake; whereas tea intake had no significant associations with GDM and PE. Conclusion: Our findings suggested that caffeine exposure in pregnancy may be protective against the development of GDM and have little to no association with PE.
Abstract 14268: Prognostic Value of Clinical and Echocardiographic Factors in Atrial Functional Tricuspid Regurgitation
Authors: Agostina M Fava, Michael Nakhla, Adel Hajj Ali, Emmanuel Akintoye, Kevser Akyuz, Zoran B Popovic, A M Gillinov, Gosta B Pettersson, Brian P Griffin, Milind Y Desai, Tom Kai Ming K Wang
Journal: Circulation (2022)

Introduction: Atrial functional tricuspid regurgitation (AFTR) is an increasingly recognized and prevalent clinical entity associated with adverse outcomes. Hypothesis: We evaluated the clinical and echocardiographic features of AFTR and those associated with poor prognosis. Methods: Consecutive patients with at least moderate-to-severe and isolated AFTR during 14 years were studied, and clinical and echocardiographic parameters including that for TR and the right heart were analyzed. Multivariable and receiver-operative characteristics analyses were performed to identify predictors and their thresholds for all-cause mortality during follow-up. Results: Amongst 155 AFTR patients (age 73±15, female 83%), 58(37%) were symptomatic, and 80 (52%) had atrial fibrillation. There were 77 (49%) deaths over a mean follow-up of 3.9±3.3 years. Multivariable analyses results are shown in the Table 1, were symptoms, right atrial strain and right ventricular systolic pressure (RVSP) were independently associated with mortality during follow-up with hazards ratios (95% confidence intervals, P-values) of 3.27 (1.18-9.04, P=0.022), 0.95 per 1% increase (0.92-0.98, P=0.01), and 1.05 per 1 mmHg increase (1.01-1.09, P=0.003). Area under curve (95% confidence interval) and optimal thresholds for the most important echocardiographic parameters to predict mortality were RVSP 0.80 (0.74-0.92) &gt;44 mmHg, right atrial strain 0.73 (0.62-0.84) &lt; +21%, and right ventricular free wall longitudinal strain 0.69 (0.57-0.81) &gt; -18%. Conclusions: Significant AFTR is associated with adverse prognosis, therefore accurate diagnosis is critical. The key predictors of mortality include symptoms, reduced right atrial strain and higher RVSP, and their presence may prompt more aggressive medical and procedural therapies in AFTR patients that warrants further research.
Abstract 12896: Case of Probable Takutsubo's Cardiomyopathy Post Intravenous Immunoglobulin Infusion for Neuromyopathy Syndrome
Authors: Tanesh K Ayyalu, Michael Goyfman
Journal: Circulation (2022)

Introduction: Takotsubo’s Cardiomyopathy (TCM) is a diagnosis of exclusion recognized by regional left ventricle (LV) dysfunction and absent coronary artery disease. There are isolated reports of patients with autoimmune conditions developing TCM post intravenous immunoglobulin (IVIG). IVIG is a plasma product which inactivates microbial antigens and downregulates certain cytokines, but its cardiac effects are varied. Our case describes a female with progressive neuromyopathy who developed cardiomyopathy post IVIG infusion. Case: A 68 year old female, with type 2 diabetes, hypertension, stroke, and neuromyopathy presented with worsening dysarthria and gait issues for 2 years. Examination revealed multiple neurological deficits, and vital signs showed pulse of 105 with blood pressure of 101/75 mmHg. Initial electrocardiogram (EKG) showed sinus tachycardia and CT angiogram of head was unremarkable. She had a negative cardiac catheterization 2 years ago and a normal echocardiogram 6 months ago. IVIG 400 mg/kg daily for 5 days was started for neuromyopathy flare. She had chest pain on infusion day 4. EKG showed ST elevation in leads V2-V4, and labs revealed troponin I of 0.96 ng/ml with proBNP of 7583 pg/mL. Echo showed LV akinesis with preserved basal segmental function suggestive of TCM. Carvedilol and losartan were started. Further ischemic work up was not done as she died from respiratory failure. Discussion: IVIG is linked to thromboembolic events including strokes and myocardial infarction (MI), but TCM is rare. Risk factors include high dose therapy (&gt;1g/kg), coronary artery disease, prior MI, smoking, diabetes, hypertension, autoimmune conditions, or hyperviscosity states. Our patient had multiple risk factors for MI post infusion including age, gender, and comorbidities. Her assessment is limited by incomplete ischemic workup. IVIG may have negative cardiac effects secondary to vasoconstrictive cytokines, arterial spasm, or increased blood viscosity, but is confounded by other factors in this case. Conclusions: IVIG has poorly described cardiac effects including possible induction of TCM. Further trials monitoring cardiac outcomes post IVIG stratified by dosage and risk would improve patient selection and education.
Abstract 13098: CircRNA-miRNA-mRNA Networks Regulate Endothelial Function in Ischemic Heart Disease
Authors: Maryam Anwar, Moumita Sarkar, Aranzazu Chamorro-Jorganes, Kerrie Ford, gianni angelini, Prakash Punjabi, Costanza Emanueli
Journal: Circulation (2022)

Introduction: Ischemic heart disease (IHD) is characterized by reduced blood supply to the myocardium and is aggravated by Type 2 Diabetes Mellitus (T2DM). Most of the RNA produced by the human genome is “non-coding” in potential and involved in regulatory processes. These include circular RNAs (circRNAs) and microRNAs (miRNAs). miRNAs bind to the 3’UTR region of their target genes and repress their expression post-transcriptionally. CircRNAs lack free ends which gives them increased stability and makes them good candidates for diagnostic biomarkers and therapeutic interventions. CircRNAs bind miRNAs via a process called “sponging” that prevents the miRNAs from binding to their target genes. This study investigates the regulatory role of circRNAs in IHD and its effect on endothelial cell (EC) function. Methods and Results: We have generated bulk RNA-seq data on whole transcriptome and small RNA using heart left ventricle (LV) biopsies of 3 groups of cardiac surgery patients: 1) and 2) suffering from IHD) with/without T2DM and 3) non-ischemic controls. Bioinformatics analysis of this data has identified significant differentially expressed circRNAs, miRNAs, and mRNAs in IHD and IHD + T2DM patients. Using available databases and tools, we have predicted “sponging associations” between circRNAs and miRNAs as well as targets of sponged miRNAs producing circRNA-miRNA-mRNA networks. Since fundamental changes in IHD include a decline in EC function, we extracted all components of the networks expressed in ECs. Of note is circNPHP1, which is upregulated in IHD + T2DM patients and in human microvascular endothelial cells (HMVECs) under hypoxic and hypoxic + high glucose (HG) conditions. Furthermore, knockdown of circNPHP1 in HMVECs leads to a significant reduction of proliferation and angiogenesis under hypoxic and hypoxic + HG conditions. The downstream miRNA and mRNA connections of circNPHP1 are currently under investigation. Conclusion: circNPHP1 expression shows concordance in clinical samples and cultured cells in response to perturbation (ischemia/hypoxia and T2DM/HG). It also seems to be playing a role in EC function restoration under these conditions and is therefore promising for further investigation into its therapeutic target potential.
Abstract 12870: Absence of LDL Measurement in Secondary Prevention is Associated With Increased Subsequent Major Adverse Clinical Event (MACE) That is Only Partially Mitigated by Statin Use
Authors: Kirk U Knowlton, Heidi T May, Tami L Bair, Jeffrey L Anderson, Donald L Lappe, Joseph B Muhlestein
Journal: Circulation (2022)

Introduction: There has been considerable discussion regarding the value of follow-up LDL-C measurements in secondary prevention of major adverse cardiac events (MACE). We therefore set out to determine in a large healthcare system whether measurement of LDL-C after an ASCVD event was associated with a difference in MACE during follow-up and whether differences in outcomes could be attributed to differences in statin use. Methods: The Intermountain Enterprise Data Warehouse was searched to identify all adults with a first encounter for ASCVD-including coronary artery disease (CAD), cerebrovascular disease (CVD), and peripheral arterial disease (PAD)—between January 1, 1995 and December 31, 2016 who survived the index event and were followed for ≥3 years or until death. Results: Patients (N=68,411) had an average age of 66±14 years; 65% were men; 70.3%, 21.0%, and 8.6% entered with CAD, CVD, and PAD, respectively. A statin was prescribed to 52% of patients during follow-up. A total of 33,698 (49%) did not have and 34,713 (51%) did have a follow-up LDL-C test prior to a subsequent MACE (death, MI, CVA, and revascularization) or end of follow-up. By 3 years, MACE occurred in 14,835 (37.4%) vs. 5,770 (20.1%) of those without vs. with an LDL-C measurement, respectively (Figure top). The multivariable hazard ratio for 3 year MACE based on measuring LDL-C was 0.47. The increased MACE rate associated with not measuring LDL-C was partially mitigated by statin use (Figure bottom). Only 44.7% vs. 58.9% of patients without vs. with LDL-C measurement were taking statins. Conclusion: These data indicate that there is a significant and clinically meaningful difference in MACE based on a follow-up measurement of LDL-C. Statin administration partially, but not completely mitigated the increased MACE rate. While these results are limited in that they are from a retrospective registry, they indicate that LDL-C should be measured, and statin should be administered after an initial ASCVD event.
Abstract 12821: Progressive Improvement in Left Ventricular Performance Associated With Progressive Regional Dyssynchrony
Authors: Bruce R Ito, Abbey M Ervin, Justina P Nguyen, Veronica Najera, Cindy Alvarez, Guy P Curtis
Journal: Circulation (2022)

Background : We have shown that non-excitatory epicardial stimulation (NES) increases measures of cardiac function mediated by local release of norepinephrine. In this further investigation we determined whether NES is accompanied by improved indices of left ventricular (LV) performance, reflected in PV loops and timing of aortic valve opening and closing. Methods : Anesthetized pigs (n=6) were instrumented with a LV high-fidelity pressure/volume conductance transducer, thoracic aortic pressure transducer, left atrial (LA)/ LV epicardial electrodes, and sonomicrometer segment length (SL) gauges placed proximal (lateral base) and distal (posterior mid LV) to the LV stimulation site. During constant LA pacing, LV pulses (0.8ms, 2-3x threshold volts) were applied during the absolute refractory period for 3 minutes (3x), before and after β-receptor blockade (BB, metoprolol). Data were analyzed at baseline, and at an estimated 30%, 60% and 100% of developed ventricular dyssynchrony (DVD) contraction pattern. Results: Consistent with earlier findings, NES resulted in an early shortening and relaxation pattern of the proximal SL manifest as an 80% decrease in the LVP vs. SL loop area in the absence of change in the remote segment. This was accompanied by an increase in peak systolic pressure and LV dP/dt max. Although NES did not change the area of the LVP vs. LV volume loop (stroke work) or alter the interval from LV electrical activation (R wave) to the onset of LV pressure increase, aortic valve opening occurred up to 14.1 ± 2.8 ms earlier (p &lt;0.01) compared to baseline. The duration of an open aortic valve slightly increased (6.0 ± 3.9 ms) whereas ejection duration from valve opening to peak Pao decreased 18.2 ± 3.0 ms (p &lt; 0.01). Conclusion : These findings demonstrate that NES elicits a local contractile dysynchrony resulting in an enhanced cardiac inotropic state characterized by more rapid global LV contraction with earlier aortic valve opening with no change in stroke work.
Abstract 13131: Three-Dimensional Echocardiography Left Atrial Appendage Dimensions is a Reflect of Cardiac Rhythm at Mid-Term Follow-Up in Atrial Fibrillation Patients
Authors: Laurie Soulat-Dufour, Theo SIMON, Sylvie Lang, Stephane EDERHY, Saroumadi ADAVANE, Marion Chauvet-Droit, Pascal Nhan, Elodie Capderou, Iris Kamami, Camille Arnaud, Pierre-Antoine Lebos, Pauline Issaurat, Franck Boccara, Ariel Cohen
Journal: Circulation (2022)

Introduction: Few studies have described the characteristics of the left atrial appendage (LAA) using three dimensional (3D) transesophageal echocardiography (TEE) in atrial fibrillation (AF). Hypothesis: We hypothesized that 3D characteristics of the LAA could further characterize patients in AF. Methods: We prospectively evaluated 156 patients hospitalized for AF with two-dimensional (2D) transthoracic and 3D TEE of the LAA within 24 hours of admission. 3D parameters were off-line analysed with Tomtec software (4D Cardio-View, Generic Volume, Philips) (Figure 1A). Patients were divided into two groups according to the cardiac rhythm at 2 years of follow up: restoration of sinus rhythm (SR group, 107 patients) or persistence of atrial fibrillation (AF group, 49 patients). Results: The mean age of the population was 66±11 years and 95 (61%) patients were male. At admission using 2D transthoracic echocardiography, AF group had in comparison with SR group higher left atrial end-systolic volume indexed (respectively 48.0 (38.7-57.0) versus 41.8 (35.0-51.5) ml/m 2 , p=0.0096), higher E velocity (respectively 0.90 (0.78-1.00) versus 0.76 (0.62-0.91) m/s, p= 0.0001) and higher pulmonary arterial pressure (respectively 31 (25-38) versus 28 (23-33) mmHg, p=0.0142). There were no significant differences in left ventricle ejection fraction and right atrial end-systolic volume indexed. At admission using 2D TEE, AF group had in comparison with SR group lower emptying flow velocity (29 (20-38) versus 38 (26-53) cm/s, p=0.002) and filling flow velocity (29 (20-39) versus 40 (29-56) cm/s, p=0.001) of the LAA. In 3D TEE, AF group had higher 3D end-systolic and end-diastolic LAA volumes (non-indexed and indexed) and no significant differences in LAA ostium in comparison with SR group (Figure 1B). Conclusions: 3D evaluation of the LAA reflects a degree of cardiac cavities remodeling in AF and seems to be associated with the evolution of cardiac rhythm at two-years follow-up.
Abstract 12854: Strategies and Outcomes of Patients With Severely Reduced Ejection Fraction (≤15%) Undergoing Transvenous Lead Extraction: A Single Center Experience
Authors: Yingyot Arora, Roger G Carrillo
Journal: Circulation (2022)

Introduction: Patients with severely reduced EF (SREF≤15%) are deferred from transvenous lead extraction (TLE) due to fears of intraoperative hemodynamic collapse. When these patients require lead extraction, their management options are limited, and they suffer high morbidity and mortality. Left ventricular assist devices may provide intraoperative hemodynamic support and facilitate TLE, enabling life-saving interventions. Hypothesis: We present our single-center experience performing TLE in 245 patients with SREF. Additionally, we report the outcomes of 8 patients who received left ventricular support during TLE. Methods: Between January 2008-January 2022, we performed TLE on 245 patients with Stage D heart failure, SREF, and Class I or II indications for extraction. Primary (clinical success and in-hospital mortality) and secondary outcomes (length of stay [LOS] and procedure-associated complications) were compared between SREF patients and control. A subgroup analysis was performed in the SREF group to evaluate the outcomes of eight patients who underwent extraction with LV assist devices. Results: Overall clinical success was high (97.6%), and mortality was low (5.3%). There were no statistically significant differences in primary outcomes associated with extraction between groups. Similarly, there were no significant differences in procedural complications between groups. In the SREF group, there were no significant differences in outcomes between the eight patients undergoing TLE with LV assist devices and cases that did use LV assist devices. Conclusions: Lead extraction in patients with SREF can be performed safely and effectively. Adopting a few simple steps, including initiating LV support, can overcome myocardial impairment in patients who decompensate.